The effect of chronic heart failure and type 2 diabetes on insulin-stimulated endothelial function is similar and additive

Britt Falskov¹, Thomas Steffen Hermann¹, Christian Rask-Madsen², Atheline Major-Pedersen¹, Buris Christiansen¹, Jakob Raunsø¹, Lars Køber³, Christian Torp-Pedersen¹, Helena Dominguez^4
1Department of Cardiology, Gentofte Hospital, Denmark; ²Joslin Diabetes Center, Boston (MA), USA; ³Department of Cardiology, Rigshospitalet, Copenhagen, Denmark; ⁴Department of Cardiology, Herlev Hospital, Herlev, Denmark

Aim: Chronic heart failure is associated with endothelial dysfunction and insulin resistance. The aim of this investigation was to study insulin-stimulated endothelial function and glucose uptake in skeletal muscles in patients with heart failure in comparison to patients with type 2 diabetes.
Methods: Twenty-three patients with systolic heart failure and no history of diabetes, seven patients with both systolic heart failure and type 2 diabetes, 19 patients with type 2 diabetes, and ten healthy controls were included in the study. Endothelial function was studied by venous occlusion plethysmography. Insulin-stimulated endothelial function was assessed after intra-arterial infusion of insulin followed by co-infusion with serotonin in three different dosages. Forearm glucose uptake was measured during the insulin infusion.
Results: Patients with systolic heart failure had impaired insulin-stimulated endothelial function. The percentage increase in blood flow during co-infusion with insulin and serotonin dose response study was 24.74% ± 6.16%, 23.50% ± 8.32%, and 22.29% ± 10.77% at the three doses respectively, compared to the healthy control group 45.96% ± 11.56%, 67.40% ± 18.11% and 84.57% ± 25.73% (P = 0.01). Insulin-stimulated endothelial function was similar in heart failure patients and patients with type 2 diabetes, while it was further deteriorated in patients suffering from both heart failure and diabetes with a percentage increase in blood flow of 19.15% ± 7.81%, -2.35% ± 11.76%, and 5.82% ± 17.70% at the three doses of serotonin, respectively. Forearm glucose uptake was impaired in patients with heart failure compared to healthy controls (P = 0.03) and tended to be further impaired by co-existence of diabetes (P = 0.08).
Conclusion: Systolic heart failure and type 2 diabetes result in similar vascular insulin resistance and reduced muscular insulin-stimulated glucose uptake. The effects of systolic heart failure and type 2 diabetes appear to be additive.

Keywords: insulin resistance, diabetes, heart failure, endothelial function